代谢相关脂肪性肝病(MAFLD)是人类健康的一大威胁,研究MAFLD具有重要的现实意义.目前认为,MAFLD的发病与脂质代谢障碍、氧化应激、炎症反应和胰岛素抵抗等因素有关;肠道菌群作为近年来的研究热点,同样参与了MAFLD的多个发病环节.过氧化物酶体增殖物激活受体(PPAR)是机体内脂质代谢和糖代谢的关键性调节因素,参与MAFLD的发病,而肠道菌群和PPAR之间亦相互作用.现就肠道菌群-PPAR信号通路在MAFLD发病中的作用研究进展进行综述.
Objective : Astragaloside IV (AS-IV) is the primary bioactive component purified from Astragalus membranaceus which is one of the traditional Chinese medicines. Research studies found that AS-IV has significant pharmacological effects on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver cirrhosis, and diabetic nephropathy, but little is known about the effects of AS-IV on nonalcoholic fatty liver disease (NAFLD). In this study, we investigated whether AS-IV has beneficial effects on NAFLD in rats and its potential mechanisms. Methods : Male SD rats were fed with high-fat diet (HFD) for 12 weeks to establish NAFLD rat model, and then, the rats were divided into five groups. The control group rats were fed with normal diet for 12 weeks and then were given normal saline (1.0 ml kg −1 day −1 ) by intragastric administration for 4 weeks. The model group rats were fed with HFD for 12 weeks and then were given normal saline (1.0 ml kg −1 day −1 ) by intragastric administration for 4 weeks. The AS-IV-L, AS-IV-M, and AS-IV-H groups were treated with 20, 40, and 80 mg kg −1 day −1 of AS-IV by intragastric administration for 4 weeks and given HFD diet. Then, we detected serum transaminase (ALT, AST), blood lipid (TG, TC), inflammatory cytokines (IL-6, IL-8 and TNF-α), liver histology(NAFLD activity score), TLR4/MyD88 signaling pathway in liver tissue. Results : We found AS-IV significantly reduced serum levels of AST, ALT, TG, TNF-α, IL-6, and IL-8 in NAFLD rats and downregulate the expression of TLR4 mRNA, MyD88 mRNA, NF-κB mRNA, and proteins in liver tissue. Moreover, AS-IV could significantly reduce the NAFLD activity score of NAFLD rat liver. Conclusion : In this study, we demonstrated that AS-IV have a protective effect on NAFLD by inhibiting TNF-α, IL-6 and IL-8 levels and down-regulating TLR4, MyD88 and NF-κB expression in rat liver tissues.
Cancer is one of the major life threatening diseases, with higher mortality rate and morbidity. It is always a challenge for effective drug delivery and release of drug in specific tumor sites. Therefore to identify the synergistic effect of chemotherapeutic drug and photo thermal agent on tumor area, Doxorubicin (DOX) acts as anticancer agent but it has low aqueous solubility so its clinical application is limited. The present study developed doxorubicin (DOX) were designed to be with the poly ethylene glycol (PEG) functionalized copper and selenium (Cu-Se) nanoparticles (PEG@Cu-Se + DOX) and it is efficiently synthesized and enhance its aqueous formulation and improve the prostate cancer (DU145 and LNCaP) activity. The characteristics like mono dispersity, size stability and constant spectral of as-synthesized nanoparticles are comparably excellent than DOX alone. Also the enhanced cellular uptake and in vitro cytoxicicty suggests these nanoparticles selectively killing prostate cancer. In this present study explained that PEG@Cu-Se + DOX as a safe and hopeful strategy for chemotherapeutics of photothermal therapy and deserve for further clinical evaluations.
The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.
OBJECTIVE To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. METHODS Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. RESULTS Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (P<0.01). The levels of serum resistin, and of resistin protein and mRNA in liver, were significantly higher in the MC group than in the NC group of rats (all P less than 0.01). The body weight of rats in the TP group was significantly lower than those in the MC group (P<0.05). The levels of serrn resistin, resistin protein and mRNA in the liver, and insulin resistance were significantly lower in the TP group than in the MC group of rats (all P<0.01). The PP group did not show significant differences in any of these measures, except for loss of body weight (P<0.05). CONCLUSION Telmisartan elicits preventive and protective effects in a NASH rat model.Telmisartan may improve insulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.